DRUG CLASS AND MECHANISM: Orlistat is a drug that promotes loss of weight by preventing the digestion and absorption of fat in food. In the intestine, an enzyme called lipase (produced primarily by the pancreas) breaks apart fat in food so that it can be absorbed into the body. Orlistat blocks the action of lipase and thereby prevents the breakup and absorption of fat. Orlistat blocks absorption of about 25% of the fat in a meal. The unabsorbed fat is excreted in the stool. The FDA approved Orlistat by prescription in 1999. alli, a lower dose formulation of orlistat, was approved for purchase without a prescription "over the counter" in 2007.

PRESCRIBED FOR: Orlistat is combined with a reduced-calorie diet to promote weight loss. Orlistat also may be used to prevent weight gain after weight has been lost. Candidates for treatment with orlistat are patients who are obese with a body mass index (a measure of obesity) of more than 30 kg/m2. Candidates also include patients with a body mass index of between 27 and 30 kg/m2 if other risk factors for arteriosclerosis are present such as high blood pressure, diabetes, and elevated blood cholesterol or triglycerides. Based on several scientific studies, the average weight loss that is achieved when orlistat is taken as recommended for six months to one year is 12.4 to 13.4 pounds.

DOSING: The recommended prescription dose for Xenical is one capsule (120 mg) three times daily. The recommended dose for alli is 60 mg three times daily. Orlistat should be taken one hour after or during a meal containing about 15 mg of fat. Meals without fat do not require orlistat. No additional benefit has been shown when orlistat was taken in doses greater than 120 mg. Patients should eat a nutritionally balanced, reduced calorie diet that contains approximately 30% of calories from fat. Alli includes an individually tailored online weight loss support program.

Some dietary vitamins bind to fat (vitamins A, D, E and beta- carotene). When orlistat is taken, these vitamins are not absorbed and are eliminated in the stool in increased amounts along with the fat. Therefore, patients taking orlistat should take a multivitamin containing these "fat-soluble" vitamins to ensure that adequate amounts of the vitamins are available for absorption. To ensure that the vitamins in the multivitamins are not bound to fat like the vitamins in the diet, the multivitamin should be taken at least two hours before or several hours after the orlistat.

DRUG INTERACTIONS: The blood thinning effect of warfarin (Coumadin) depends on the amount of vitamin K in the body, and vitamin K is one of the vitamins that bind to fat. Patients receiving warfarin who begin orlistat should have their blood clotting monitored closely because the orlistat may cause levels of vitamin K to decline. This will increase the effects of warfarin and lead to abnormal bleeding from the warfarin. There is no evidence that a deficiency of vitamin K occurs in patients who are taking orlistat.

Orlistat may reduce the absorption and blood levels of cyclosporine (Sand immune) when both drugs are administered together. Therefore, cyclosporine should be administered two hours before or after orlistat, and more frequent monitoring of cyclosporine levels may be needed.

Hypothyroidism has been reported when orlistat and levothyroxine were combined.� Patients treated with both orlistat and levothyroxine should be monitored for changes in thyroid function.� the orlistat and levothyroxine should be taken at least four hours apart.

PREGNANCY: Safe use of orlistat during pregnancy has not been established. Therefore, orlistat is not recommended during pregnancy.

NURSING MOTHERS: It is not known if orlistat is secreted in breast milk. Therefore, it probably should not be taken by nursing mothers.

SIDE EFFECTS: The most common side effects of orlistat are oily spotting on underwear, flatulence, urgent bowel movements, fatty or oily stools, increased number of bowel movements, abdominal pain or discomfort, and inability to control stool (incontinence). Between 1 in 250 and 1 in 70, patients experienced one or more of these symptoms in the first year. Generally, the side effects occurred within three months of starting therapy. In about 50% of patients, the side effects resolved within one to four weeks, but the effects in some patients lasted six months or longer. To reduce the occurrence of these side effects, meals should contain no more than 30% fat because it is the unabsorbed fat that causes most of the symptoms. Alli causes fewer side effects because it contains half the dose of prescription-strength orlistat. Patients receiving orlistat with a history of oxalate kidney stones may develop increased levels of oxalate in their urine, which may increase the risk of kidney stones.

USES: This medication is used along with a doctor-approved reduced-calorie diet, exercise, and behavior modification program to help significantly overweight (obese) persons lose weight. Taking orlistat can also help prevent you from regaining the weight you have lost. Losing weight and keeping it off can reduce the many health risks that come with obesity, including heart disease, diabetes, high blood pressure, some forms of cancer, certain breathing problems, and a shorter lifespan. Dietary fats need to be broken down into smaller pieces before the body can absorb them. Orlistat works by blocking the enzyme that breaks down fats in your diet. This undigested fat then passes out of your body in your bowel movement. Orlistat does not block the absorption of calories from sugar and other non-fat foods, so you still need to restrict your total intake of calories.

HOW TO USE: Read the Patient Information Leaflet provided by your pharmacist before you start taking orlistat and each time you get a refill. If you have any questions, consult your doctor or pharmacist. Take this medication by mouth with liquid sometime during each main meal that contains fat or within 1 hour after the meal, usually 3 times daily or as directed by your doctor. If you occasionally miss a meal or your meal contains no fat, skip that dose of the medication. To decrease the chance of unpleasant side effects, it is very important that no more than 30% of the calories in your diet come from fat. Your daily intake of fat, protein, and carbohydrate should be evenly spread over three main meals. Because this drug can interfere with the absorption of certain vitamins (fat-soluble vitamins including A, D, E, K), a daily multivitamin supplement containing these nutrients is recommended. Take the multivitamin at least 2 hours before or 2 hours after taking orlistat (e.g., at bedtime).If you take cyclosporine, take it at least 2 hours before or after orlistat to make sure the full dose of cyclosporine is absorbed into your bloodstream. If you take levothyroxine, take it at least 4 hours before or after orlistat. You should see some weight loss within 2 weeks after you start orlistat. Tell your doctor if your condition does not improve or if it worsens.